The invention relates to automatic analyzing apparatus in which a liquid sample is to be tested, usually chemically, and the results of the test related to the identity of the liquid sample.
The invention herein is primarily related to the testing of biological samples such as blood, but is not so limited.
Diagnosis, preventative medicine and information concerning the efficacy of treatment are greatly aided in modern medical practice by making a myriad of tests on blood. These tests may be divided into two major categories, physical and chemical. The physical tests are accomplished by operating on the whole blood and the chemical tests are performed by operating on the blood serum, that is, the liquid which remains after the blood cells have been separated therefrom.
The physical tests include counting and sizing the white and red cells, measuring the prothrombin time of the blood, measuring the hematocrit, etc.
The chemical tests are performed by adding certain reagents to the serum, subjecting the resulting solution to certain temperatures for particular times and then making colorimetric measurements of absorbence of certain monochromatic light. In some tests, the solution is sprayed into a flame and the resulting color is measured. In some tests reactions are measured at intervals to give dynamic data.
The information which can be obtained by means of tests of the chemical type include ascertaining the quantitative amounts of organic and inorganic substances in the blood, turbidity with respect to certain substances, etc. Some of these tests are identified as follows:
cholesterol PA0 protein PA0 chloride radical PA0 urea PA0 uric acid PA0 bilirubin PA0 sugar PA0 calcium PA0 sodium PA0 enzymes of different kinds PA0 gamma globulin PA0 various organic acids PA0 hemoglobin
and many others.
The invention is primarily directed to novel apparatus for making chemical tests, but as will be pointed out, physical tests can be made as well. In such cases, the sample prepared from whole blood is not necessarily centrifuged, but will be diluted and, if necessary lysed. The diluted sample can be automatically passed to a cell counting and sizing apparatus for making a determination of the red blood cell population and/or a lysed diluted sample can be automatically passed to such apparatus for determination of the white blood cell population.
The chemical tests are normally made by adding a reagent to a serum sample, incubating it for a given time at a given temperature and then measuring the absorbency of the sample with respect to monochromatic light passed through the same. Apparatus are available, and such are contemplated by the invention, in which there is a dip tube or snorkel which may be automatically dipped into a sample container, sucks a quantity of the sample into a test cuvette, projects light from a spectrophotometer comprising part of the apparatus through the cuvette and reads out the absorbency in absorbence units by means by suitable photoresponsive means and electrical circuitry converting the electrical output of the photoresponsive means into a signal that has been logarithmically operated upon by the circuit to give a linear response. The wave length of the incident light is adjusted by the operator prior to setting the apparatus in operation, but this can be done automatically as described hereinafter.
The apparatus of the invention is an automatic analyzing device in which a plurality of samples is passed through the machine and each sample is tested and the results are provided as one of the outputs of the device.
Such apparatus, per se, is well known but the nature and characteristics of such known apparatus have inherent disadvantages which the invention herein obviates. Ultimately, the ends sought by the invention herein are greater reliability, economy, simplicity and a higher throughout than prior machines, even those which are much larger and more sophisticated than that to be described and claimed. The manner in which these ends are accomplished is inherent in the structure and method of operation of the apparatus of the invention which differs considerably from that which is known as will be apparent.
To understand and appreciate the invention, it will be valuable to discuss the structure and operation of automatic analyzing apparatus which are known at the present time.
Known apparatus are of the so-called single channel and multiple channel variety. This designation "channel" is used to signify a test which is being run. Thus, a single channel apparatus will handle a single sample and will perfrom one test on that sample. The operator feeds a plurality of samples in suitable containers to the machine and the machine moves the samples through the procedure which has been established, either by the construction of the apparatus or by adjustments made thereto, and the output of the machine comprises the results of these tests produced by the apparatus one at a time.
Multiple channel machines use a single sample which is transferred to a plurality of reaction vessels and the respective reaction vessels go through individual tests and provide a plurality of test results each of which is independent of the other but all of which are related to a single sample.
In each of the above apparatus there are variations. Some apparatus provide means for handling different tests in a single channel machine so that each sample fed to the machine will be tested in a different manner. For example, a package of reagents may be furnished for any one of a large number of tests and the machine automatically constructed to run the test which is chosen by the operator with the package automatically running through the test and producing the desired results. Any other single channel machine must be changed in its operation in case it is desired to change the test from the current one being run to another.
As for the multiple channel devices, some give test choices by eliminating selected ones of the entire apparatus repertoire; some require all tests to be performed on all samples regardless of need.
All of the above machines have a characteristic which is wasteful of time and wasteful of the capability of automatic apparatus. This is the fact that the sample is transported through the machine and the test performed at a speed which is fixed by the construction of the machine. The speed is determined by the time that is required for the longest test to be made. The samples and/or reaction vessels are moved through these machines on belts, chains, wheels, or through tubes at a constant rate. If a reaction is to require more time than another, the first reaction is started earlier along the path of movement so that all testing is done at a single location.
The functions which are to be performed in these automatic machines include adding reagents to the samples, incubating, mixing, transferring treated samples to colorimeters, etc. Added to these functions, in multiple channel machines which use reaction vessels, the vessels have to be washed, rinsed and returned to the beginning of a path of movement.
The principal difference between the present apparatus and those of the prior art, as will be appreciated from the detailed description which follows, is that the present apparatus operates asynchronously. There is no preset cycle of operations which must be followed by every sample; no continuously moving chain or belt or series of racks; no specific order of processing the samples; and no handling and/or recycling of the same reagent containers or vessels. Each sample is tested individually on a shared time basis, the apparatus operating asynchronously and automatically in that said sample follows a predetermined procedure, which if it includes any delay, enables the apparatus to be gainfully occupied during the course of such delay. An important structure provided by such apparatus is a carriage or pair of carriages moving along a guideway and engaged in handling the sample containers throughout their testing procedures. The carriages pick up the samples and carry them to the appropriate zones where functions are performed, depositing them where required in storage zones for incubation at ambient or other temperatures for predetermined times. If the delay or delays resulting are substantial, the apparatus remembers the position of deposit, times the length of resulting delay and while such time is passing performs other functions. For example, a carriage may return to the initial zone where it picks up another sample, enters its code into the memory of the program and control mechanism, moves the sample container to the reagent-adding zone where it adds a totally different reagent or the same reagent as in the first sample, and then deposits this second container in another position of the storage zone -- again remembering the location of the deposit and the time required. If in the meantime the time for the first sample to have been incubated has been used up, one or the other of the carriages will move to the storage zone, pick up the first sample container, carry it to the testing zone where it will be tested and generally move it through the procedure which has been predetermined for it. The said procedure is predetermined and programmed by suitable instructions which have been electronically stored in the memory of the programming and control device and coded to the test code carried on indicia means attached to the particular sample container.
One can visualize the apparatus of the invention in operation as a machine which includes one or more carriages rapidly moving back and forth along a guideway carrying out multiple testing of a plurality of samples in respective sample containers. The containers are picked up and moved and deposited in accordance with procedures which overlap and are intermixed in time so that there is no continuous or cyclical movement. The equivalent would be an infallible chemist with a prodigious memory, or two such chemists with their memories connected in the case of an apparatus having two carriages, scurrying back and forth, picking up samples, processing them, remembering where they are and how long they are to be there, testing the, recording results, etc., all intermixed by properly timed in accordance with procedures for the test codes that the infallible chemists have together memorized. No time is wasted, no delay permitting other processing is permitted to pass, and everything is done efficiently and with complete identification as a result of which the maximum number of tests is done in the minimum of time but with the least amount of apparatus.